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Apo E-Epsilon 4 Confers Attentional Benefits In Early Adulthood

December 3, 2012

The same allele that quadruples the risk of Alzheimer’s disease also was associated with some aspects of improved cognition in early adulthood in a prospective study that measured attention during cognitive tasks performed during brain MRI scans.

People who carried the high-risk allele, the apolipoprotein E (apo E) epsilon-4 allele, were more focused – and stayed focused longer – than were non–epsilon-4 carriers. They also showed significantly more activity in brain areas associated with attention- and task-related cognition, Jennifer Rusted, Ph.D., and her colleagues reported (NeuroImage 2013;65:364-73).

“We speculate that [positive epsilon-4 status] may also index genotype differences in cholinergic system activity, for example, higher tonic acetylcholine levels,” wrote Dr. Rusted of the University of Sussex, England, and her coauthors.

The study cohort comprised 41 subjects, 21 of whom were epsilon-4 positive. Their mean age was 21 years. They underwent testing with the National Adult Reading Test (which measures verbal IQ), the Rapid Visual Information Processing task (which measures capacity for sustained attention), and a covert attention task (which measures ability to reorient attention). The last two tasks were performed in an MRI scanner.

The study also examined task-related brain activation based on functional MRI measurement of blood oxygenation level dependent according to cognitive test, and included previously obtained white matter imaging.

The epsilon 4–positive subjects significantly outperformed epsilon 4–negative subjects on all components of each attention task, with more correct detections, fewer errors, and a longer attention span.

Those findings correlated with brain activity. The positive subjects showed greater activation of the supplementary motor area, parietal regions, frontal gyrus, medial temporal lobe, and parahippocampus.

Diffusion tensor imaging showed significantly higher axial diffusivity – thought to be a measure of axonal integrity – among epsilon 4–positive than -negative volunteers. “Improved white matter integrity in epsilon 4–positive [subjects] suggests better communication between brain regions, driving increases in the observed functional activity,” the authors wrote.

Studies of similar attention tests in mice have shown that superior performance is associated with higher tonic acetylcholine levels, the authors noted. “On this basis, the behavioral advantages we have observed in epsilon 4–positive [subjects] could indicate a difference in acetylcholinesterase tonic activity.”

The study was sponsored by a grant from the U.K. Biotechnology and Biological Sciences Research Council. None of the authors declared any financial conflicts.



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